FMO3 Gene: Flavin Containing Dimethylaniline Monoxygenase 3
Genetic and Functional Insights into FMO3, a Key Enzyme in Drug Metabolism and Trimethylaminuria
Gene Information Card
| Symbol | FMO3 |
|---|---|
| Full Name | Flavin Containing Dimethylaniline Monoxygenase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 1q24.3 |
| NCBI Gene ID | 2328 ncbi.nlm.nih.gov/gene/2328 |
| Ensembl ID | ENSG00000107949 |
| UniProt ID | P31513 |
| OMIM ID | 136132 |
| HGNC ID | 3812 |
| Aliases | FMOII, TMAU, dJ127D3.1 |
Description
FMO3 encodes flavin-containing monooxygenase 3, an enzyme primarily expressed in the liver that catalyzes the oxidation of nucleophilic heteroatom-containing compounds, including drugs and dietary amines. It is critical for the metabolism of trimethylamine (TMA) to trimethylamine N-oxide (TMAO). Loss-of-function mutations cause trimethylaminuria (fish odor syndrome).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Trimethylaminuria (TMAU) | Loss-of-function mutations in FMO3 impair conversion of TMA to TMAO, leading to accumulation of malodorous TMA in sweat, urine, and breath. | ClinVar, OMIM #136132 |
| Primary trimethylaminuria | Autosomal recessive inheritance; over 40 pathogenic variants reported. | OMIM #602079 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 27.4 | High |
| Kidney | 2.1 | Low |
| Small intestine | 1.8 | Low |
| Lung | 0.5 | Not detected |
| Brain | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK293 | 0.8 | Low expression |
| A549 | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.472G>A (p.Glu158Lys) | Missense | Common in TMAU | Loss of function |
| c.923A>G (p.Asn308Ser) | Missense | Common in TMAU | Loss of function |
| c.1498G>A (p.Gly500Arg) | Missense | Rare | Loss of function |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic FMO3 mutations reduce or abolish enzyme activity, causing trimethylaminuria.
Gain of Function (GOF)
No gain-of-function mutations reported in FMO3.
Dominant Negative (DN)
No dominant-negative mutations reported; disease is recessive.
View complete mutation data：
Gene Ontology (GO)
| • monooxygenase activity (GO:0004497) | • NADP binding (GO:0050661) |
| • xenobiotic metabolic process (GO:0006805) | • epoxygenase P450 pathway (GO:0019373) |
| • mitochondrion (GO:0005739) |
Pathways
• Drug metabolism - cytochrome P450 (Reactome R-HSA-211981)
• Biological oxidations (Reactome R-HSA-1430728)
• Metabolism of xenobiotics by cytochrome P450 (KEGG hsa00980)
Protein Summary
FMO3 is a 532-amino acid microsomal flavoprotein that uses FAD and NADPH to oxygenate soft nucleophiles. It is highly expressed in adult liver and plays a major role in the detoxification of dietary and microbial-derived amines. Structural variants in the FMO3 gene are the primary cause of trimethylaminuria.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FMO3 Knockout HEK293 Cell Line | EDJ-KQ4616 | Human | 2328 | Details Get a Quote |
| FMO3 Knockout HeLa Cell Line | EDJ-KQ53255 | Human | 2328 | Details Get a Quote |
| FMO3 Knockout A-549 Cell Line | EDJ-KQ61737 | Human | 2328 | Details Get a Quote |
| FMO3 Knockout HCT 116 Cell Line | EDJ-KQ70224 | Human | 2328 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
